phase 1/2 study of the combination of pixantrone, etoposide, bendamustine and, in cd20 positive tumors, rituximab in patients with relapsed aggressive non-hodgkin lymphomas of b- or t-cell phenotype - the p[r]eben study

Conditions: Malignant Lymphoma

Summary: this is a phase 1/2 open label study to assess the safety and efficacy of pixantrone in combination with bendamustine, etoposide and , for cd20 positive b-cell lymphomas, rituximab (p\[r\]eben), in patients with relapsed anhl of b- or t-cell phenotype.

this is a phase 1/2 open label study to assess the safety and efficacy of pixantrone in combination with bendamustine, etoposide and , for cd20 positive b-cell lymphomas, rituximab (p\[r\]eben), in patients with relapsed anhl of b- or t-cell phenotype.

Eligibility criteria:
inclusion criteria: * patients with a histologically confirmed relapse of an aggressive lymphoma of t- or b-cell phenotype (including follicular lymphoma grade 3b). for excluded histological entities see 'exclusion criteria' * phase 1 + phase 2 'fit' patients: * age 18-70 years at the time of inclusion * ecog ps 0-1 at protocol entry * deemed 'fit' by the treating physician * phase 2 'frail' patients: * age 71-85 years at the time of inclusion and/or * ecog ps 2-3 at protocol entry and/or * deemed 'frail' by the treating physician * at least six months response duration since last given course of treatment * estimated life expectancy of 3 months or longer * measurable disease * hemoglobin ≥ 8 g/dl (≥5 mmol/l) * platelets ≥ 100 x 109/l; ≥ 75 x 109/l permitted if bone marrow involvement * absolute neutrophil count ≥ 1.5 x 109/l; ≥ 1.0 x 109/l permitted if documented bone marrow involvement * serum bilirubin ≤ 1.5 x upper limit of normal (uln); patients with proven gilbert's syndrome (≤ 5 x uln) may be enrolled. * serum glutamic-oxaloacetic transaminase (ast) and/or serum glutamic-pyruvic transaminase (alt) ≤ 2.5 x uln, or ≤ 5 x uln if elevation is due to hepatic involvement by lymphoma * serum creatinine ≤ 2 x ulnb * women of childbearing potential must use safe anticonception (e.g. contraceptive pills, intrauterine devices etc.) during the study and 12 months after the last administration of study drugs * male patients must use contraception for the duration of the study and 6 months after the last administration of study drugs if his partner is of childbearing potential * written informed consent exclusion criteria: * patients with primary refractory disease (e.g. progressing under platinum-containing or similar salvage therapy) defined as \< 6 months response duration from last given course of treatment. * high-dose therapy with autologous stem cell rescue within the last 6 months prior to study entry. * following t-cell lymphoma entities: * t-cell lymphoblastic lymphoma * hepatosplenic t-cell lymphoma * extranodal nk/t, nasal type * subcutaneous panniculitis-like * primary cutaneous t-cell lymphoma * primary leukemic t-cell lymphoma * following b-cell lymphoma entities: * transformed indolent b-cell lymphomas * post-transplant b-cell lymphoproliferative disease * hiv-associated b-cell lymphoma * concurrent severe and/or uncontrolled medical disease which is not lymphoma-related * left ventricular ejection fraction (lvef) \< 45% * suspected or documented central nervous system involvement by nhl * patients known to be antigen positive for hiv and/or hepatitis b and/or hepatitis c * patients with active, uncontrolled infections * vaccination with live, attenuated vaccines within 4 weeks of inclusion * pregnant and/or breastfeeding women * history of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma * known hypersensitivity to one or more of the study drugs * unwillingness or inability to comply with the protocol